Naphtho(2,1-e)(1,2,4)thiadiazine 1,1-dioxides



United States Patent NAPHTHO[2,1-e][1,2,4]THIADIAZlNE 1,1-DIOX1DES Peter H. L. Wei, Upper Darby, and Stanley C. Bell,

Narberth, Pa., assignors to American Home Products Corporation, New York, N.Y., a corporation of Delaware No Drawing. Filed May 12, 1967, Ser. No. 637,927 Int. Cl. C07d 93/08; A611: 27/00 US. Cl. 260-243 10 Claims ABSTRACT OF THE DISCLOSURE The present invention is concerned with ZH-naphtho [2,1-e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxides; 4H- naphtho[2,1-e] [1,2,4] thiadiazine-7-sulfonamide 1,1-dioX- ides; and 3,4 dihydro-2H-naphtho[2,1-e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxides which are pharmacologically active as diuretics.

OzNHRs i S OzNHRa Patented Aug. 12, 1969 wherein R and R are both selected from the group consisting of hydrogen, halogen and lower alkyl; R is selected from the group consisting of hydrogen, lower alkyl, phenyl, lower alkylphenyl, lower alkoxyphenyland phen (lower) alkyl.

The compounds of this invention depicted by the above Formula A are properly designated: 3,4-dihydro-2H- naphtho[2,1-e][1,2,4-]thiadiazine-7-sulfonarnide 1,1 dioxides, such as, 3,4-dihydro-3-methyl-2H-naphtho[2,1e] [l,2,4]thiadiazine-7-sulfonamide 1,1-dioxide; 3,4-dihydro- 8-methyl-3-pheny1-2H-naphtho[2,1-e] [1,2,4] thiadiazine-7- sulfonarnide 1,1-dioXide and 8-chloro-3,4-dihydro-3-(4- tolyl) -2H-naphtho [2,1-e] 1,2,4] thiadiazine-7-sulfonamide 1,1-dioxide.

Those compounds of this invention represented by the above Formula B are called: 2H-naphtho[2,1-e] [1,2,4]thiadiazine-7-sulfonamide 1,1-dioXides, for example, 2H-naphtho[2,1-e][1,2,4]thiadiazine 7 sulfonamide 1,1-dioxide; 6-chloro 2H naphtho [2,1-e] [1,2,4] thiadiazine-7-sulfonamide 1,1-dioxide and 2-methyl-2H- naphtho[2,1-e] [1,2,4]thiadiazine 7 methylsulfonamide 1,1-dioxide.

When the compounds of this invention are depicted by the above Formula C, they are called: 4H-naphtho [2,1-e] [1,2,4] thiadiazine-7-sulfonamide 1,1-dioxides, such as, 4 methyl-4H-naphtho[2,l-e] [1,2,4]thiadiaZine-7-sulfonamide 1,1-dioxide; 8-ch1oro-3,4-dimethyl-4H-naphtho [2,1-e] [1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide, and 8-chloro-3 ,4-diethyl-4H-naphtho [2,1-e] [1,2,4] thiadiazine- 7-ethylsulfonamide 1,1-dioxide.

When the R substituent attached to the thiadiazine moiety of the compounds of the present invention represented by Formulae B and C is hydrogen, these structures represent tautomeric forms of particular compounds of this invention which co-exist in a state of equilibrium. Whenever compounds of this invention exist as tautomers, they will be designated as 2H-naphtho[2,1-e] [1,2,4]thiadiazine-7-sulfonamide 1,1-dioxides. It is understood, however, that these compounds also co-exist in the corresponding 4H naphtho[2,1-e] [1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide tautomeric forms.

The 3,4 dihydro-ZH-naphtho [2,1-e] [1,2,4]thiadiazine- 7-su1fonamide 1,1-dioxides (A) of the present invention may be prepared by the process which is illustrated by the following schematic equation:

5 wherein R R R and R are defined as above. The

cyclization reaction is efiected by contacting a Z-amino- 3 naphthalene-1,5-disu1fonamide (I) with ,an aldehyde .(II) in an alkanol at about steam bath temperatures for a period of about one-half hour to about four hours. Preferably this reaction is conducted in ethanol at 100 C. for a period of one-half hour.

When the cyclization reaction is complete, the product (A) is separated by standard recovery procedures, for example, filtration, concentration and recrystallization from a suitable solvent, e.g. an aqueous alkanol mixture. In this manner, there is obtained the appropriate 3,4-dihydro-2H-naphtho[2,1-e] [1,2,4]thiadiazine-7-su1fonamide 1,1-dioxides (A).

The 3 unsubstituted-ZI-I-naphtho[2,l-e] [1,2,4]thiadiazine-7-sulfonamide 1,1-dioxides (B1) and the 3-unsubsituted 4H naphtho [2,1-e][1,2,4]thiadiaZine-7-sulfonamide 1,1-dioxides (C1) which represent a portion of the compounds represented by above Formulae B and C respectively are prepared by the process which is depicted by the following reaction scheme:

wherein R R and R are defined as above, with the proviso that at least one of the two R substituents on the [B] ring of the Z-aminonaphthalene-l,S-disulfonamide reactant (III) is hydrogen. The cyclization reaction is effected by refluxing an appropriate 2-aminonaphthalene- 1,5-disulfonamide (III) with formic acid (IV) for a period of about eight to about twenty-four horus. Preferably this reaction is conducted at reflux temperatures for about sixteen hours.

When the reaction is complete, the product is recovered by conventional procedures, e.g. filtration and recrystallization from a suitable solvent, such as a dimethylformamide-ethanol mixture. In this manner, there is obtained the appropriate product. For example, when both R substituents of the reactants [B] ring are hydrogen, the product is a tautomeric mixture of the 3-unsubstituted- 2H-naphtho[2,1-e] [1,2,4]thiadiazine-7 sulfonamide 1,1-

dioxide (B-1) and 3-unsubstituted-4H naphtho[2,1-e]

[1,2,4] thiadiazine-7-sulfonamide 1,1-dioxide (C-l when the R substitutent of the l-sulfamoyl (SO NHR [B] ring moiety is hydrogen and the R substituent of the 2- amino (-NHR [B] ring moiety is other than hydrogen, the product is the appropriate 3-unsubstituted-4H-naphtho [2,1-e][1,2,4]thiadiazine 7 sulfonamide 1,1 dioxide (01) and when the R substituent of the 2-a.rnino (NHR [B] ring moiety is hydrogen and the R substituent of the 1-sulfamoyl (SO NHR [B] ring moiety is other than hydrogen, the product is the appropriate l t-unsubstituted 2H naphtho[2,1-e][1,2,4]thiadiazine-7- sulfonamide 1,1-dioxide (B1).

The 3-substituted-2H-naphtho[2,1-e] [1,2,4]thiadiazine- 7-sulfonamide 1,1-dioxides (B2) and the 3-substituted- 4H naphtho[2,l-e] [1,2,4]thiadiazine-7-sulfonamide 1,1- dioxides (C-2) which comprise the remaining portion of the compounds represented by above Formulae B and C respectively are. synthesized by the process which is illustrated in the following reaction sequence:

slozNHRa NRSG O Cyclization R1 l S OzNHRg 3 N N 02s 02s F I I a FAQ R2 Haggis l 1 SOzNHRz V SOzNHRz (3-2 wherein R R R and R are defined as above, with the proviso that at least one of the two R substituents on the [B] ring of the 2-acylamidonaphthalene-1,S-disulfonamide reactant (V) is hydrogen and that R; is other than hydrogen. The cyclization reaction is effected by admixing an appropriate 2-acylamidonaphthalene-l,S-disulfonamide (V) with concentrated ammonium hydroxide for a period of about forty-eight hours at room temperature. When the reaction is complete, the resulting product is obtained by standard recovery procedures, such as, concentration and recrystallization from a suitable solvent, e.g. an alkanol. In this manner, there is obtained the appropriate product. For example, when both R substituents of the reactants [B] ring are hydrogen, the product is a mummeric mixture of the appropriate 3-substituted-2H-naphtho [2,l-e][l,2,4]thiadiazine 7 sulfonamide 1,1 dioxide (B-2) and 3-substituted-4H naphtho[2,1-e][1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide (0-2); when the R substituent of the 1-sulfamoyl (-SO NHR [B] ring moiety is hydrogen and the R substituent of the 2-acylamido (NR COR [B] ring moiety is other than hydrogen, the product is the appropriate 3-substituted-4H- naphtho[2,1-e][1,2,4]thiadiazine 7 sulfonamide 1,1- dioxide (0-1); and when the R substituent of the 2- acylamido (NR COR [B] ring moiety is hydrogen and the R substituent of the l-sulfamoyl (SO NHR ['B] ring moiety is other than hydrogen, the product is the appropriate 3 substituted 2H naphtho[2,l-e] [1,2,4] thiadiazine-7-sulfonamide 1,1-dioxide (B-1).

The reactants employed in the synthesis of the compounds of the present invention are prepared by procedures well known in the art.

Some of the reactants employed in the synthesis of the compounds of the present invention are known compounds which are commercially available while others are prepared by procedures well known in the art. The 2- amino-naphthalene 1,5 disulfonamide reactants (I) and (III) may be prepared by reacting a Z-aminonaphthalene sulfonic acid or a 2-amino-1,5-naphthalene disulfonic acid with chlorosulfonic acid and/ or thionyl chloride to aiford an appropriate 2-amino-1,5-naphtha1ene disulfonyl chloride which is then reacted with ammonium hydroxide or an amine to aflord the desired 2-aminonaphthalene 1,5- disulfonamide (I) and (III). Specific examples and reaction conditions are hereinafter given in Examples I and II. Alternatively, the 2-acylamido-naphthalene-1,S-disulfonamides (V) may be prepared by the general procedure described by Novello et al. in the J.A.C.S. vol. 25, p. 970 (1960).

In accord with the present invention, the new naphtho [2,1-e][1,2,4]thiadiazine '1,1'- dioxides herein described have been found to possess interesting pharmaceutical properties which render them useful as synthetic medi cinals. More particularly, these compounds, in standard pharmacological tests, have exhibited utility as central nervous system depressants.

When the compounds of this invention are employed as central nervous system depressants they may be administered alone or in combination with pharmaceutically acceptable carriers, the proportion of which is determined by the solubility and chemical nature of the compound, chosen route of administration and standard pharmaceutical practice. For example, they may be administered orally in the form of tablets or capsules containing such excipients as starch, milk sugar, certain types of clay and so forth. They may be administered sublingually in the form of troches or lozenges in which the active ingredient is mixed with sugar and corn syrups, flavoring agents and dyes; and then dehydrated sufficiently to make it suitable for pressing into a solid form. They may be administered orally in the form of solutions which may contain coloring and flavoring agents or they may be injected parenterally, that is intramuscularly, intravenously or subcutaneously. For parenteral administration they may be used in the form of a sterile solution containing other solutes, for example, enough saline or glucose to make the solution isotonic.

The dosage of the present therapeutic agents will vary with the form of administration and the particular compound chosen. Furthermore, it will vary with the particular subject under treatment. Generally, treatment is initiated with small dosages substantially less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under the circumstances is reached. It will generally be found that when the composition is administered orally, larger quantities of the active agent will be required to produce the same effect as a smaller quantity given parenterally. In general, the compounds of this invention are most desirably administered at a concentration level that will generally afford efiective results without causing any harmful or deleterious side effects and preferably at a level that is in the range of from about 5 to about 50 mg./kilo/ day, although as aforementioned variations will occur. However, a dosage level that is in the range of from about to about 35 mg./kilo/day is most desirably employed in order to achieve efiective results.

The following examples are given by way of illustration and are not to be construed as limitations of this invention, many variations of which are possible without departing from the scope and spirit thereof.

Example I To cold chlorosulfonic acid (200 ml.), there is slowly added 100 g. of Z-aminonaphthalene sulfonic acid. The solution is heated on a steam bath for one hour and then cooled. Thionyl chloride (100 ml.) is slowly added and the solution is again heated on a steam bath for two hours. The mixture is slowly poured into ice and the solid material collected, washed with water and dried at room temperature. The crude material is recrystallized from benzene to afford 2-amino-l,5-naphthalene disulfonyl chloride (50 g.), M.P. 163-5 C. (decomp.).

Analysis.-Calcd. for C H Cl NO S C, 35.30; H, 2.08; Cl, 20.90; N, 4.12; S, 18.83. Found: C, 35.17; H, 1.94; Cl, 21.2; N, 4.11; S, 18.3. 7

Alternatively, 2-amino-l,5-naphthalene disulfonic acid (200 g.) is added to 450 ml. of chlorosulfonic acid. The solution is heated on a steam bath for one hour and then cooled. To the cold solution 200 ml. of thionyl chloride is gradually added and the resulting mixture heated on a steam bath for one-half hour. The resulting solution is poured onto ice and well stirred. The solid is collected, washed with water and dried. The crude material is recrystallized from chloroform to afford 2-amino-1,5-naphthalene disulfonyl chloride (115 g.).

Example II 2-amino-1,5-naphthalene disulfonyl chloride as prepared in Example I (50.0 g.) is dissolved in an alcoholic ammonium hydroxide solution (300 ml. NH OH and ml. ethanol) and the solution heated on a steam bath for one hour. The solid is collected (22 g.) and recrystallized from ethanol to afford 2-aminonaphthalene-l,S-disulfonamide, M.P. 226-230" C.

Analysis.Calcd. for C10H11N304S2: C, H, N, 13.97; S, 21.25. Found: C, 40.09; H, 3.68; N, 13.67; S, 21.4.

Example III 2-aminonaphthalene-l,S-disulfonamide (5.0 g.), as prepared in Example II, is suspended in ethanol and heated on a steam bath with 6 ml. of acetaldehyde for 30 minutes. Some insoluble material is removed by filtration, the filtrate concentrated and the solid collected (3.5 g.). The crude material is recrystallized from an aqueous alcohol solution to yield 3,4 dihydro-3-methyl2H-naphtho [2,l-e] [1,2,4] thiadiazine-7-sulfonamide l,l-dioxide, M.P. 263-5 C.

Analysis.Calcd. for C12H13N304S2: C, H, N, 12.83; S, 19.57. Found: C, 44.31; H, 3.90; N, 12.63; S, 19.7.

Example IV 2-aminonaphthalene-1,S-disulfonamide (5.0 g.) is heated to reflux in 10 ml. of formic acid overnight. The white solid (4.0 g.) is collected and recrystallized from a mixture of dimethylformamide-ethanol to afford ZH-naphtho [2,1-e][1,2,4]thiadiazine-7-sulfonamide l,l-dioxide, M.P. 365 C. (dec.).

Analysis.-Calcd. for S11H9N3O4S21/2 C, 43.15; H, 3.62; N, 14.09; S, 18.44. Found: C, 43.36; H, 4.01; N, 13.95; S, 17.9.

Example V 2-amino-6-methyl-1,5-naphthalene disulfonic acid (100 g.) is added to 225 ml. of chlorosulfonic acid. The solution is heated on a steam bath for one hour and then cooled. To the cold solution 100 ml. of thionyl chloride is gradually added and the mixture heated on a steam bath for one-half hour. The resulting solution is poured onto ice and the mixture stirred well. The solid is collected, washed with water, dried and recrystallized from chloroform to afford 2-amino-6-methyl-1,S-naphthalene disulfonyl chloride.

The above prepared 2-amino-6-methyl-l,S-naphthalene disulfonyl chloride (25.0 g.) is dissolved in an alcoholic ammonium hydroxide solution ml. NH OH and 50 m1. ethanol) and the solution heated on a steam bath for one hour. The solid is collected and recrystallized from ethanol to aflord 2-amino-6-methylnaphthalene-1,5-disulfonamide. v

This 2-amino-6-methylnaphthalene-1,5 disulfonamide (2.5 g.). is suspended in ethanol and heated on a steam bath with 3 ml. of benzaldehyde for thirty minutes. Some insoluble material is removed by filtration and the filtrate concentrated, the solid collected and then recrystallized from an aqueous alcohol solution to afford 3,4-dihydro- 8 methyl-3-phenyl-2H-naphtho[2,1-e] [1,2,4]thiadiazine- 7-sulfonamide-l,1-dioxide.

In a similar manner, 8-chloro-3,4-dihydro-3-(4-tolyl)- 2H naphtl1o[2,1-e][1,2,4]thiadiazine 7 sulfonamide l,l-dioxide is prepared.

Example VI Z-amino-l-methylsulfamoylnaphthalene 5-sulfonamide (10.0 g.) is suspended in ethanol and heated on a steam bath with 12 ml. of acetaldehyde for one hour. Some insoluble material is filtered off, the filtrate concentrated and the solid collected. The crude material is recrystallized from an aqueous ethanol solution to afford 3,4-dihydro- 2,3-dimethyl-2H-naphtho[2,l-e] [1,2,4]thiadiazine-7 sulfonamide l,l-dioxide.

Similarly, Z-amino-l-ethylsulfamoyl naphthalene-S-ethylsulfonamide is reacted with propionaldehyde to afford 2,3 diethyl-3,4-dihydro-2H-naphtho[2,1-e][1,2,4]thiadiazine-7-ethylsulfonamide 1,1-dioxide.

Example VII Repeating the procedure of Example VI to react an ap propriate Z-aminonaphthalene-l,5-disulfonamide with an aldehyde the following 3,4-dihydro-2H-naphtho[2,1-e] [1,2,4]thiadiazine-7-sulfonamide 1,1-dioxides are produced:

8-bromo-3,4-dihydro-2,3-dimethyl 2H naphth[2,l-e] [1,2,4] thiadiazine-7-methylsulfonarnide 1,1-dioxide;

3 ethyl 5,9 difiuoro-3,4-dihydro-2H-naphtho[2,1-e] [1,2,4] thiadiazine-7-methylsulfonamide 1,1-dioxide;

6-chloro-2,4-diethyl-3,4-dihydro 2H naphtho[2,l-e] [1,2,4] thiadiazine-7-sulfonamide 1,1-dioxide;

3,4 dihydro propyl-2H-naphtho[2,l-e] [1,2,4] thiadiazine-7-sulfonamide 1,1-dioxide;

3,6-diethyl-3,4-dihydro-2H naphtho[2,1-e] [1,2,4] thiadiazine-7-sulfonamide 1,1-dioxide and 3,4 dihydro 8 methyl-2H-naphtho[2,1-e] [1,2,4]thiadiazine-7-propylsulfonamide 1,1-dioxide.

Example VIII 2-amino-4-chloronaphthalene-1,S-disulfonamide (10 g.) is heated to reflux in ml. of formic acid for twelve hours. Thereafter, the solid is collected and recrystallized from a mixture of dimethylformamide-ethanol to afford 6-ch1oro-2H-naphtho[2,l-e][1,2,4]thiadiazine-7 sulfonamide 1,1-dioxide.

Repeating the above procedure utilizing appropriate reactants, the following compounds are prepared:

2 methyl 2H naphtho[2,1-e] [1,2,4]thiadiazine 7- methylsulfonamide 1,1-dioxide;

2 propyl 2H-naphtho[2,1-e] [1,2,4]thiadiazine-7-sulfonamide 1,1-dioxide;

9-ethyl-2-methyl-2H naphtho [2,1-e] [1,2,4] thiadiazine- 7-sulfonamide 1,1-dioxide; and

6-bromo-2 ethyl-2H-naphtho[2,1-e] [1,2,4]thiadiazine- 7-ethylsulfonamide 1,1-dioxide.

Example IX Example X Z-methylaminonaphthalene-1,S-disulfonamide (2.5 g.) is heated to reflux in 5 ml. of formic acid for ten hours. Thereafter, the solid is collected and recrystallized from dimethylformamide methanol to yield 4 methyl 4H- naphtho[2,1-e][1,2,4]thiadiazine-7- sulfonamide 1,1-dioxide.

Rep ating the above procedure to react the hereinafter listed Z-aminonaphthalene disulfonamides with formic acid, the following products are obtained:

Product 4-ethyl-4H-naphtho[2,1-e][1,2,4] thiadiazine-7sulionamide 1,1- dioxide.

8-chloro-4-methyl-4H-naphtho [2,1-e][1,2,4]thiadiazine-7- methylsulionamide 1,1-dioxide.

6-bromo+propyl-4H-naphth0 [2,1-e][1,2,4]thiadiaziue-7- propylsulfouamide 1,1-di0xido.

Reactant 2-ethylaminonaphthalene-l,5-

disulfonamides.

t-rehloro-z-nicthylamino-S-methylsulfamcylnaphthalene-1-sulfonamidc.

4-bromo-2-propylamino-S-propylsulaluoylnaplitlialcue-l-sulfoua- 1111 0.

Example XI 2-acetamido 6 chloronaphtha'lene-1,5-disul'fona1nide (1.0 g.) in 25 m1. of concentrated ammonium hydroxide is allowed to stand at room temperature for forty-eight hours and then concentrated to dryness under vacuum. The residue is recrystallized from ethanoyl to afford 8- chloro 3 methyl-2H-naphtho[2,1-e] [1,2,4]thiadiazine- 7-sulfonamide 1,1-dioxide.

Similarly, 2-benzamido-6-bromonaphthalene 1,5-disulfonamide is converted to 8-bromo-3-phenyl-2H-naphtho [2,1-e] [1,2,4] thiadiazine-7-sulfonamide 1,1-dioxide.

Example XII 2 acetamido-G-chloro-1-methylsulfamoylnaphthalene- 5-sulfonamide (2.0 g.) in 50 ml. of concentrated ammonium hydroxide is allowed to stand at room temperature for thirty hours and then evaporated to dryness under vacuum. The residue is recrystallized from methanol to yield 8-chloro-2,3-dimethyl-2H-naphtho[2,l-e] l,2,4]thiadiazine-7-sulfonamide 1,1-dioxide.

Similarly, 2 benzamido-G-bromo 1 methylsulfamoylnaphthalene-S-sulfonamide is converted to 8-bromo-2- methyl 3-phenyl-2H-naphtho[2,1-e] [1,2,4]thiadiazine-7- sulfonamide 1,1-dioxide.

Example XIII '2 (N methylacetamido) 6-chloronaphthalene-l,5- disulfonamide (1.0 g.) in 25 ml. of concentrated ammonium hydroxide is allowed to stand at room temperature for forty hours and then evaporated to dryness. The residue is recrystallized from ethanol to afford 8-chloro- 3,4 dimethyl 4H-naphtho[2,l-e][1,2,4-]thiadiazine-7- sulfonamide 1,1-dioxide.

Similarly, 2-(N-methylbenzamido)-6=bromosulfamoylnaphthalene 5 sulfonamide is converted to 8-bromo-4- methyl 3 phenyl-4H-naphtho[2,1-e] [1,2,4]thiadiazine- 7-sulfonamide 1,1-dioxide.

Example XIV Repeating the procedure of Examples XI to XIII, the following compounds are prepared:

8 chloro 2,3 diethyl 2H naphtho [2,1-e] [1,2,4] thiadiazine-7-ethylsulfonamide 1,1-dioxide;

8 chloro 3,4 diethyl 4H-11aphth0[2,1-e][1,2,4] thiadiazine-7-ethy1sulfonamide 1,1-dioxide;

2 methyl-3 (4 tolyl) 2H naphtho[2,1-e] [1,2,4] thiadiazine-7-sulfonam-ide 1,1-dioxide;

4 methyl 3 (4 tolyl)-2H-naphtho[2,l-e][1,2,4] thiadiazine-7-sulfonamide 1,1-dioxide; and

8 fiuoro 3 (4-methoxyphenyl)-2H-naphtho[2,1-e] [1,2,4] thiadiazine-7-sulfonamide 1,1-dioxide.

What is claimed is:

1. A compound selected from the group consisting of those having the formulae:

SO3NHR3 and I S OzNHRa wherein R and R are both selected from the group consisting of hydrogen, halogen and lower alkyl; R; is

selected from the group consisting of hydrogen and 2 2. 3,4 'dihydro 3 methyl-2H-naphtho[2,l-e] [1,2,4j thiadiaz-ine-7-sulfonamide 1,1-dioxide.

3. 2H naphtho[2,1-e] [1,2,4] thiadiazine-7-sulfonamid 1,1-dioxide.

4. 3,4 dihydro 8 methyl 3 phenyl 2H naphth [2, l-e] 1,2,4] thiadiazine-7-sulfonamide 1,1-dioxide.

5. 8 chloro 3,4 d-ihydro 3 (4-tolyl)-2H-naphth( [2,l-e] [1,2,4] thiadiazine-7-sulfonamide l,1-dioxide.

6. 3,4 dihydro 2,3 dimethyl 2H naphtho[2,1-ej [1,2,4] thiadiazine-7-sulfonamide 1,1-dioxide.

7. 6 chloro 2H naphtho[2,1 e] [1,2,4]thiadiazine 7-sulfonamide 1,1-dioxide.

8. 3,4 dihydro 3 (4 methoxyphenyl)-2H-naphth [2,1-e] [1,2,4]thiadiazine7-sulfonamide 1,1-dioxide.

9. 4 methyl 4H naphtho[2,1-e][1,2,4]thiadiazine 7-su1fonamide 1,1-dioxide.

10. 8 chloro 4 methyl 4H-naphtho[2,1-e] [1,2,4j thiadiazine-7-methylsulfonamide 1,1-dioxide.

References Cited UNITED STATES PATENTS 3,257,395 6/1966 Griot. 3,277,086 10/ 1966 Wei et a1.

NICHOLAS S. RIZZO, Primary Examiner US. Cl. X.R. 424-246 

